Ruthenium-catalysed multicomponent synthesis of the 1,3-dienyl-6-oxy polyketide motif.

Polyketide natural products are an important class of biologically active compounds. Although substantial progress has been made on the synthesis of repetitive polyketide motifs through the iterative application of a single reaction type, synthetic access to more diverse motifs that require more than one type of carbon-carbon bond connection remains a challenge. Here we describe a catalytic, multicomponent method for the synthesis of the privileged polyketide 1,3-dienyl-6-oxy motif. The method allows for the formation of two new carbon-carbon bonds and two stereodefined olefins. It generates products that contain up to three contiguous sp3 stereocentres with a high stereoselectivity in a single operation and can be used to generate chiral products. The successful development of this methodology relies on the remarkable efficiency of the ruthenium-catalysed alkene-alkyne coupling reaction between readily available vinyl boronic acids and alkynes to provide unsymmetrical 3-boryl-1,4-diene reagents. In the presence of carbonyl compounds, these reagents undergo highly diastereoselective allylations to afford the desired 1,3-dienyl-6-oxy motif and enable complex polyketide synthesis in a rapid and asymmetric fashion.

Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Substituted 1 H-Indoles and Tryptophan Derivatives with Vinylcyclopropanes.

Vinylcyclopropanes (VCPs) are known to generate 1,3-dipoles with a palladium catalyst that initially serve as nucleophiles to undergo [3 + 2] cycloadditions with electron-deficient olefins. In this report, we reverse this reactivity and drive the 1,3-dipoles to serve as electrophiles by employing 3-alkylated indoles as nucleophiles. This represents the first use of VCPs for the completely atom-economic functionalization of 3-substituted 1 H-indoles and tryptophan derivatives via a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA). Excellent yields and high chemo-, regio-, and enantioselectivities have been realized, providing various indolenine and indoline products. The method is amenable to gram scale and works efficiently with tryptophan derivatives that contain a diketopiperazine or diketomorpholine ring, allowing us to synthesize mollenine A in a rapid and ligand-controlled fashion. The obtained indolenine products bear an imine, an internal olefin, and a malonate motif, giving multiple sites with diverse reactivities for product diversification. Complicated polycyclic skeletons can be conveniently constructed by leveraging this unique juxtaposition of functional groups.

Ru-catalyzed sequence for the synthesis of cyclic amido-ethers.

Efficient synthesis of versatile building blocks for enabling medicinal chemistry research has always challenged synthetic chemists to develop innovative methods. Of particular interest are the methods that are amenable to the synthesis of chemically distinct and diverse classes of pharmaceutically relevant motifs. Herein we report a general method for the one-pot synthesis of cyclic α-amido-ethers containing different amide functionalities including lactams, tetramic acids and amino acids. For the incorporation of the nucleotide bases, a chemo and regioselective palladium-catalyzed transformation has been developed, providing rapid access to nucleoside analogs.

Isomerization of N-Allyl Amides To Form Geometrically Defined Di-, Tri-, and Tetrasubstituted Enamides.

Enamides represent bioactive pharmacophores in various natural products, and have become increasingly common reagents for asymmetric incorporation of nitrogen functionality. Yet the synthesis of the requisite geometrically defined enamides remains problematic, especially for highly substituted and Z-enamides. Herein we wish to report a general atom economic method for the isomerization of a broad range of N-allyl amides to form Z-di-, tri-, and tetrasubstituted enamides with exceptional geometric selectivity. This report represents the first examples of a catalytic isomerization of N-allyl amides to form nonpropenyl disubstituted, tri- and tetrasubstituted enamides with excellent geometric control. Applications of these geometrically defined enamides toward the synthesis of cis vicinal amino alcohols and tetrasubstituted α-borylamido complexes are discussed.

Ruthenium-catalyzed alkene-alkyne coupling of disubstituted olefins: application to the stereoselective synthesis of trisubstituted enecarbamates.

The Ru-catalyzed alkene-alkyne coupling reaction has been demonstrated to be an enabling methodology for the synthesis of complex molecules. However, to date, it has been limited to monosubstituted olefins. Herein we report the first general utilization of disubstituted olefins in the Ru-catalyzed alkene-alkyne coupling reaction by employing carbamate directing groups. The products are stereodefined trisusbstituted enecarbamates. The elaboration of these structures toward the asymmetric synthesis of complex aminocyclopentitols and 1,2-amino alcohols is discussed.

Sustainability metrics: life cycle assessment and green design in polymers.

This study evaluates the efficacy of green design principles such as the "12 Principles of Green Chemistry," and the "12 Principles of Green Engineering" with respect to environmental impacts found using life cycle assessment (LCA) methodology. A case study of 12 polymers is presented, seven derived from petroleum, four derived from biological sources, and one derived from both. The environmental impacts of each polymer's production are assessed using LCA methodology standardized by the International Organization for Standardization (ISO). Each polymer is also assessed for its adherence to green design principles using metrics generated specifically for this paper. Metrics include atom economy, mass from renewable sources, biodegradability, percent recycled, distance of furthest feedstock, price, life cycle health hazards and life cycle energy use. A decision matrix is used to generate single value metrics for each polymer evaluating either adherence to green design principles or life-cycle environmental impacts. Results from this study show a qualified positive correlation between adherence to green design principles and a reduction of the environmental impacts of production. The qualification results from a disparity between biopolymers and petroleum polymers. While biopolymers rank highly in terms of green design, they exhibit relatively large environmental impacts from production. Biopolymers rank 1, 2, 3, and 4 based on green design metrics; however they rank in the middle of the LCA rankings. Polyolefins rank 1, 2, and 3 in the LCA rankings, whereas complex polymers, such as PET, PVC, and PC place at the bottom of both ranking systems.